Neuronal ageing is promoted by the decay of the microtubule cytoskeleton

• DOI: 10.1371/journal.pbio.3002504
• Publication Date: 2024-03-13T17:45:52Z
• Authors: Pilar Okenve-Ramos; Rory Gosling; Monika Chojnowska...; Kriti Gupta; Samuel Shields; Haifa Alhadyian; Ceryce Collie; Emilia Gregory; Natalia Sanchez-S...
• Keywords: Cognitive Decline

Natural ageing is accompanied by a decline in motor, sensory, and cognitive functions, all impacting quality of life. Ageing also the predominant risk factor for many neurodegenerative diseases, including Parkinson’s disease Alzheimer’s disease. We need to therefore gain better understanding cellular physiological processes underlying age-related neuronal decay. However, gaining this slow process due large amount time required age mammalian or vertebrate animal models. Here, we introduce new model within Drosophila brain, which report classical hallmarks previously observed primate brain. These include axonal swellings, cytoskeletal decay, reduction calibre, morphological changes arising at synaptic terminals. In fly these begin occur few weeks, ideal study mechanisms ageing. discovered that decay microtubule (MT) cytoskeleton precedes onset other hallmarks. showed MT-binding factors Tau, EB1, Shot/MACF1, are necessary MT maintenance axons synapses, their functional loss during triggers bundle followed Furthermore, genetic manipulations improve networks slowed down confer aged specimens ability outperform age-matched controls. Our work suggests key lesion site neurons offers promising target advanced age.